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c-myc癌基因在人肺癌细胞系中的扩增与表达。

Amplification and expression of the c-myc oncogene in human lung cancer cell lines.

作者信息

Little C D, Nau M M, Carney D N, Gazdar A F, Minna J D

出版信息

Nature. 1983;306(5939):194-6. doi: 10.1038/306194a0.

Abstract

Genetic changes involving the c-myc oncogene have been observed in human tumours. In particular, the c-myc gene is translocated in Burkitt's lymphoma and is amplified in the human promyelocytic leukaemia cell line, HL-60, which contains double minute chromosomes (DMs). More recently, an amplified c-myc gene has been positioned on a chromosomal homogeneous staining region (HSR) in a human colon cancer cell line, COLO 320, with neuroendocrine properties. Furthermore, c-myc is expressed in increased amounts in some human tumour lines, and in some cases, human small cell lung cancers (SCLC) contain DMs and HSRs. These findings prompted us to study the c-myc gene and its RNA expression in a series of human lung cancer cell lines. We now report amplification and expression of the c-myc oncogene in a system other than B-cell lymphomas, namely human lung cancer. Of 18 human lung cancer cell lines tested, 8 showed an amplified 12.5-kilobase (kb) EcoRI c-myc DNA band. Of particular interest are five SCLC lines with a high degree of c-myc DNA amplification (20-76-fold) and greatly increased levels of c-myc RNA. All five lines reside in the variant class of SCLC (SCLC-V) characterized by altered morphology, lack of expression of some SCLC-differentiated functions and more malignant behaviour than pure SCLC. Three of the five lines which have been karyotyped also contain DMs or HSRs. The finding of a greatly amplified c-myc gene in all cell lines of the SCLC-V class examined strongly suggests a role for the c-myc gene in the phenotypic conversion and malignant behaviour of human lung cancer.

摘要

在人类肿瘤中已观察到涉及c-myc癌基因的遗传变化。特别是,c-myc基因在伯基特淋巴瘤中发生易位,在含有双微体染色体(DMs)的人早幼粒细胞白血病细胞系HL-60中被扩增。最近,一个扩增的c-myc基因定位于具有神经内分泌特性的人结肠癌细胞系COLO 320的染色体均匀染色区(HSR)上。此外,c-myc在一些人类肿瘤细胞系中表达量增加,在某些情况下,人类小细胞肺癌(SCLC)含有DMs和HSRs。这些发现促使我们研究一系列人肺癌细胞系中的c-myc基因及其RNA表达。我们现在报告c-myc癌基因在除B细胞淋巴瘤以外的系统即人肺癌中的扩增和表达。在测试的18个人肺癌细胞系中,8个显示出12.5千碱基(kb)的EcoRI c-myc DNA条带被扩增。特别令人感兴趣的是5个小细胞肺癌细胞系,它们具有高度的c-myc DNA扩增(20 - 76倍)以及c-myc RNA水平大幅增加。所有这5个细胞系都属于小细胞肺癌变异型(SCLC-V),其特征是形态改变、一些小细胞肺癌分化功能的表达缺失以及比纯小细胞肺癌更具恶性行为。已进行核型分析的5个细胞系中的3个也含有DMs或HSRs。在所检测的所有SCLC-V类细胞系中发现高度扩增的c-myc基因,强烈提示c-myc基因在人肺癌的表型转化和恶性行为中起作用。

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